A Phase 1b/2a, open-label single ascending doses and multiple ascending doses study in participants with Pi*ZZ AATD

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Wave Life Sciences Ireland Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08], Diseases [C] - Digestive System Diseases [C06], Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

6 Jan 2025 → ongoing

Decision date (initial)

2024-12-03

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Wave Life Sciences UK Limited

External identifiers

EU CT number

2024-511981-36-00

WHO UTN

U1111-1311-8996

ClinicalTrials.gov

NCT06405633

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Dose response, Pharmacokinetic, Safety

To evaluate the safety and tolerability of WVE-006 in participants with Pi*ZZ AATD

Secondary objectives 2

1. To evaluate the pharmacodynamics (PD) effect of WVE-006
2. To evaluate the pharmacokinetics (PK) of WVE-006 after a single dose and following repeat doses in AATD participants

Conditions and MedDRA coding

Alpha-1 antitrypsin deficiency (AATD)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Healthy as determined by the Investigator, based on a medical evaluation, or has mild to moderate AATD-induced lung disease (FEV1 ≥50%) and/or stable mild AATD-induced liver disease (≤F2 (≤10 kPa)) on FibroScan.
2. Genetic testing confirming Pi*ZZ.
3. Participant has been a non-smoker for at least 1 year prior to screening.

Exclusion criteria 11

1. Participant has a history of multiple drug allergies or of allergic reaction to an oligonucleotide or to N-acetylgalactosamine (GalNAc).
2. Participant has a history of intolerance or any medical condition that might interfere with subcutaneous injections.
3. Any ongoing or recent infections.
4. Any recent or planned vaccinations during the study.
5. Participant has a history of regular alcohol consumption exceeding 14 standard drinks/week.
6. Unwilling to abstain from alcohol for 48 hours prior to dosing at each of the dosing visits.
7. Any recent or planned major surgery during the study.
8. Participant has any medical condition or social circumstance that, in the opinion of the Investigator, would make the participant unsuitable for participation in the study or for dosing on Day 1, or could interfere with the assessments of safety, pharmacodynamics, or pharmacokinetics, or completion of the study.
9. Participant currently on AAT augmentation therapy, planned to be on augmentation therapy anytime during the study, or has been on augmentation therapy within 30 days prior to Screening Visit.
10. Donation of blood or blood products in excess of 500 mL within 12 weeks prior to Screening Visit and/or unwilling to refrain from blood donation for the duration of the study.
11. Participant has received an investigational agent within 3 months of the Screening Visit.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The proportion of participants with adverse events.

Secondary endpoints 6

1. Single Ascending Dose - Change from baseline in levels of serum M-AAT protein.
2. Multiple Ascending Dose - Change from baseline in levels of serum M-AAT protein
3. Single Ascending Dose - Area under the plasma concentration time curve for WVE-006 from time of dosing to the last measurable concentration (AUClast)
4. Single Ascending Dose - Maximum concentration of WVE-006 in plasma
5. Multiple Ascending Doses - Area under the plasma concentration time curve for WVE-006 from time of dosing to the last measurable concentration (AUClast)
6. Multiple Ascending Doses - Maximum concentration of WVE-006 in plasma (Cmax)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Wave Life Sciences Ireland Limited

Sponsor organisation

Wave Life Sciences Ireland Limited

Address

1 Spencer Dock

City

Dublin 1

Postcode

D01 X9R7

Country

Ireland

Scientific contact point

Organisation

Wave Life Sciences Ireland Limited

Contact name

Clinical Operations

Public contact point

Organisation

Wave Life Sciences Ireland Limited

Contact name

Clinical Operations

Third parties 16

Locations

2 EU/EEA countries · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 19 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications